Differential contribution of CB1, CB2, 5-HT1A, and PPAR-gamma receptors to cannabidiol effects on ischemia-induced emotional and cognitive impairments

Author(s)

Mori, Marco Aurelio ^[1] ; Meyer, Erika ^[1] ; da Silva, Francielly F. ^[1] ; Milani, Humberto ^[1] ; Guimaraes, Francisco Silveira ^[2] ; Oliveira, Rubia Maria Weffort ^[1]

Affiliation

^[1] Univ Estadual Maringa, Dept Pharmacol & Therapeut, Ave Colombo 5790, BR-87020900 Maringa, Parana - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Pharmacol, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: European Journal of Neuroscience; v. 53, n. 6 FEB 2021.
• Web of Science Citations: 0

Abstract

An ever-increasing body of preclinical studies has shown the multifaceted neuroprotective profile of cannabidiol (CBD) against impairments caused by cerebral ischemia. In this study, we have explored the neuropharmacological mechanisms of CBD action and its impact on functional recovery using a model of transient global cerebral ischemia in mice. C57BL/6J mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min and received vehicle or CBD (10 mg/Kg) 0.5 hr before and 3, 24, and 48 hr after reperfusion. To investigate the neuropharmacological mechanisms of CBD, the animals were injected with CB1 (AM251, 1 mg/kg), CB2 (AM630, 1 mg/kg), 5-HT1A (WAY-100635, 10 mg/kg), or PPAR-gamma (GW9662, 3 mg/kg) receptor antagonists 0.5 hr prior to each injection of CBD. The animals were evaluated using a multi-task testing battery that included the open field, elevated zero maze, Y-maze (YM), and forced swim test. CBD prevented anxiety-like behavior, memory impairments, and despair-like behaviors induced by BCCAO in mice. The anxiolytic-like effects of CBD in BCCAO mice were attenuated by CB1, CB2, 5-HT1A, and PPAR-gamma receptor antagonists. In the YM, both CBD and the CB1 receptor antagonist AM251 increased the exploration of the novel arm in ischemic animals, indicating beneficial effects of these treatments in the spatial memory performance. Together, these findings indicate the involvement of CB1, CB2, 5-HT1A, and PPAR-gamma receptors in the functional recovery induced by CBD in BCCAO mice. (AU)

• FAPESP's process: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support type: Research Projects - Thematic Grants